Gastric cancer with brain metastasis: from molecular characteristics and treatment.

Gastric cancer is one of the cancers with increasing incidence and ranks fourth globally among the most frequent causes of cancer-related mortality. Early gastric cancer is often asymptomatic or presents with atypical symptoms, and the majority of patients present with advanced disease upon diagnosis. Brain metastases are present in approximately 1% of gastric cancer patients at the time of diagnosis, which significantly contributed to the overall mortality of the disease worldwide. Conventional therapies for patients with brain metastases remain limited and the median overall survival of patients is only 8 months in advanced cases. Recent studies have improved our understanding of the molecular mechanisms underlying gastric cancer brain metastases, and immunotherapy has become an important treatment option in combination with radiotherapy, chemotherapy, targeted therapy and surgery. This review aims to provide insight into the cellular processes involved in gastric cancer brain metastases, discuss diagnostic approaches, evaluate the integration of immune checkpoint inhibitors into treatment and prognosis, and explore the predictive value of biomarkers in immunotherapy.

Associations of parental age at pregnancy with adolescent cognitive development and emotional and behavioural problems: a birth cohort in rural Western China.

BACKGROUND: The relationship between parental age at pregnancy and offspring development in low- and middle-income countries remains unclear. We aimed to examine the associations of parental age at pregnancy with adolescent development in rural China. METHODS: We conducted a prospective birth cohort study of offspring born to pregnant women who participated in an antenatal micronutrient supplementation trial in rural Western China. Adolescent cognitive development and emotional and behavioural problems were assessed by using the Wechsler Intelligence Scale for Children-IV and the Youth Self-Report-2001, respectively. After accounting for the possible nonlinear relationships, we examined the linear associations between parental age (in years) at pregnancy and scores of adolescent cognitive development and emotional and behavioural problems by performing generalized estimating equations. RESULTS: Among 1897 adolescents followed from birth to early adolescence, 59.5% were male with a mean age of 11.8 (standard deviation (SD): 0.8) years. The mean ages of mothers and fathers at pregnancy were 24.6 (SD: 4.4) and 27.9 (SD: 4.1) years old, respectively. All the P values of the nonlinear terms between parental age and adolescent development in all domains were greater than 0.05. Each one-year increase in maternal age at pregnancy was associated with a 0.29-point (95% confidence interval (CI) 0.06, 0.52) increase in the full-scale intelligence quotient in early adolescence. After parental age was categorized into quartiles, the total behavioural problem scores of adolescents with fathers with an age in the fourth quartile (Q4) were 6.71 (95% CI 0.86, 12.57) points higher than those of adolescents with fathers with an age in the first quartile (Q1), with a linear trend P value of 0.01. Similarly, higher scores (worse behavioural problems) were observed for internalizing behavioural problems and other emotional and behavioural symptoms related to anxiety, withdrawal, social problems, thought problems and aggressive behaviour. CONCLUSIONS: At conception, older maternal age was independently linked to better adolescent cognitive development, whereas advanced paternal age was independently associated with a greater risk of adolescent emotional and behavioral problems. These findings suggest that public health policies targeting an optimal parental age at pregnancy should be developed in the context of offspring developmental consequences.

Associations between gestational weight gain under different guidelines and adverse birth outcomes: A secondary analysis of a randomized controlled trial in rural western China.

Several gestational weight gain (GWG) guidelines have been established based on monocenter or multicenter researches. We aimed to examine the associations between categories of GWG under the Institute of Medicine (IOM) recommendation guideline, the Chinese National Health Commission (NHC) guideline, and weight-gain-for-gestational-age z-scores derived from the INTERGROWTH-21st Project and adverse birth outcomes. We used data from an antenatal micronutrient supplementation trial in rural western China between 2002 and 2006. Maternal weekly average GWG during the second and third trimesters was calculated and classified into inadequate, adequate and excessive GWG according to the IOM and NHC, respectively. Weight-gain-for-gestational-age z-scores derived from the INTERGROWTH-21st Project were grouped into three subgroups using two approaches: z-score percentile<25th, 25th to 75th, >75th and z-score <-1, -1 to 1, >1 SD. Infant birth weight and gestational age were measured using standard approaches. Generalized linear model with binomial family and logit link was applied to estimate the odds ratio (OR) and 95% confidential intervals (CI) for GWG categories and adverse birth outcomes. Among 1,239 women with normal weight (18.5 kg/m2 to 23.9 kg/m2) during early pregnancy, 18.0% and 34.2% were classified as adequate GWG according to IOM and NHC, respectively. Less than half of Chinese women reached optimal GWG by any recommendation guideline. According to NHC, excessive GWG showed a significant association with macrosomia (OR 3.75, 95% CI 1.03, 13.74), large-for-gestation-age (LGA) (OR 2.12, 95% CI 1.01, 4.45), and inadequate GWG was associated with post-term birth (OR 2.25, 95% CI 1.21, 4.16), compared with adequate GWG. Inappropriate GWG was associated with adverse birth outcomes even among women with normal weight during early pregnancy. The monitoring and interventions of weight status during pregnancy, especially for the second and third trimesters, are of great public health importance for optimal birth outcomes. Additionally, developing guideline of appropriate GWG ranges should account for the traits of regional population.

Identification of prognosis-related lncRNAs and cell validation in lung squamous cell carcinoma based on TCGA data.

Objective: To discern long non-coding RNAs (lncRNAs) with prognostic relevance in the context of lung squamous cell carcinoma (LUSC), we intend to predict target genes by leveraging The Cancer Genome Atlas (TCGA) repository. Subsequently, we aim to investigate the proliferative potential of critical lncRNAs within the LUSC milieu. Methods: DESeq2 was employed to identify differentially expressed genes within the TCGA database. Following this, we utilized both univariate and multivariate Cox regression analyses to identify lncRNAs with prognostic relevance. Noteworthy lncRNAs were selected for validation in cell lines. The intracellular localization of these lncRNAs was ascertained through nucleocytoplasmic isolation experiments. Additionally, the impact of these lncRNAs on cellular proliferation, invasion, and migration capabilities was investigated using an Antisense oligonucleotides (ASO) knockdown system. Results: Multivariate Cox regression identified a total of 12 candidate genes, consisting of seven downregulated lncRNAs (BRE-AS1, CCL15-CCL14, DNMBP-AS1, LINC00482, LOC100129034, MIR22HG, PRR26) and five upregulated lncRNAs (FAM83A-AS1, LINC00628, LINC00923, LINC01341, LOC100130691). The target genes associated with these lncRNAs exhibit significant enrichment within diverse biological pathways, including metabolic processes, cancer pathways, MAPK signaling, PI3K-Akt signaling, protein binding, cellular components, cellular transformation, and other functional categories. Furthermore, nucleocytoplasmic fractionation experiments demonstrated that LINC00923 and LINC01341 are predominantly localized within the cellular nucleus. Subsequent investigations utilizing CCK-8 assays and colony formation assays revealed that the knockdown of LINC00923 and LINC01341 effectively suppressed the proliferation of H226 and H1703 cells. Additionally, transwell assays showed that knockdown of LINC00923 and LINC01341 significantly attenuated the invasive and migratory capacities of H226 and H1703 cells. Conclusion: This study has identified 12 candidate lncRNA associated with prognostic implications, among which LINC00923 and LINC01341 exhibit potential as markers for the prediction of LUSC outcomes.

How the marketing practices of commercial milk formula companies impact infant breastfeeding practices in China.

BACKGROUND: The marketing practices used by commercial milk formula (CMF) companies undermine breast feeding. However, it remains unclear how specific types of marketing practices result in suboptimal breast feeding. OBJECTIVES: We aimed to examine the associations of CMF marketing practices with breastfeeding outcomes, determine the influencing pathways, how it changes the perceptions and attitudes of mothers towards CMF, and how it impacts breastfeeding outcomes. METHODS: A cross-sectional survey was conducted in Beijing and Jinan, China that mapped the CMF marketing practices in 2020. Mothers were interviewed about the feeding practices for the youngest child under the age of 18 months. Maternal attitude towards CMF was assessed using a set of five questions. Six common CMF marketing practices were reviewed. A logistic regression was performed to examine the associations between the CMF marketing practices and predominant breast feeding, with adjustments for maternal age, education, occupation, socioeconomic class and caesarean section. Furthermore, a path analysis was conducted to explore the pathways between the CMF marketing practices, maternal attitude towards CMF and predominant breast feeding. RESULTS: A total of 750 mothers were interviewed, with 20.0% of mothers predominantly breast feeding their young children. Two marketing practices, online engagement with CMF companies and promotions and discounts, were statistically associated with a lower likelihood of predominant breast feeding, with an adjusted ORs of 0.53 (95% CI 0.35 to 0.82) and 0.45 (95% CI 0.22 to 0.92). Furthermore, per CMF marketing practice increase mothers concurrently exposed to was associated with a 0.79 (95% CI 0.68 to 0.92) times lower likelihood of predominant breast feeding. In addition, online engagement and free formula samples distributed in hospitals had indirect effects on suboptimal breastfeeding outcomes, which was partly mediated by positive maternal attitude towards CMF. CONCLUSIONS: CMF marketing practices were associated with a lower likelihood of optimal breastfeeding through influencing the maternal attitude towards CMF.

Platelet count and gastric cancer susceptibility: A Mendelian randomization study.

The objective of this study was to ascertain the potential causal linkage between platelet (PLT) counts and the incidence of gastric cancer (GC). This study employed a 2-sample Mendelian randomization (MR) approach, utilizing the inverse variance weighting, weighted median, and MR-Egger regression methodologies. The publicly accessible summary statistics dataset from the genome-wide association study pertaining to individuals of European ancestry (n = 145,648) was employed as the foundational resource for the exposure variable. Concomitantly, the non-cancer disease codes for GC (n = 6563), derived from individuals within the UK Biosample Bank, were utilized as the outcome measure. A set of 132 single-nucleotide polymorphisms exhibiting genome-wide significance were selected as instrumental variables, drawn from the genome-wide association studies focused on PLT counts. The application of the weighted median methodology yielded indications suggesting the possible absence of a causal relationship between PLT counts and GC (beta = 0.139, SE = 0.079, P = .077). Contrarily, the implementation of the inverse variance weighting technique produced results indicative of a potential causal relationship between PLT counts and GC (beta = 0.128, SE = 0.049, P = .009). The assessment of Cochran Q test and the scrutiny of funnel plots unveiled no discernible indications of heterogeneity or asymmetry, thus signifying the absence of directional pleiotropy. The outcomes derived from the MR analysis lend credence to the hypothesis that there exists a plausible causal relationship between erythrocyte pressure and an elevated susceptibility to gastric cancer.

Development and Validation of the Oxidative Stress Related lncRNAs for Prognosis in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell cancer (ESCC) is an aggressive disease associated with a poor prognosis. Long non-coding RNAs (lncRNAs) and oxidative stress play crucial roles in tumor progression. We aimed to identify an oxidative stress-related lncRNA signature that could predict the prognosis in ESCC. In the GSE53625 dataset, we identified 332 differentially expressed lncRNAs (DElncRNAs) between ESCC and control samples, out of which 174 were oxidative stress-related DElncRNAs. Subsequently, seven oxidative stress-related DElncRNAs (CCR5AS, LINC01749, PCDH9-AS1, TMEM220-AS1, KCNMA1-AS1, SNHG1, LINC01672) were selected based on univariate and LASSO Cox to build a prognostic risk model, and their expression was detected by RT-qPCR. The model exhibited an excellent ability for the prediction of overall survival (OS) and other clinicopathological traits using Kaplan-Meier (K-M) survival curves, receiver operating characteristic (ROC) curves, and the Wilcoxon test. Additionally, analysis of infiltrated immune cells and immune checkpoints indicated differences in immune status between the two risk groups. Finally, the in vitro experiments showed that PCDH9-AS1 overexpression inhibited proliferation ability and promoted apoptosis and oxidative stress levels in ESCC cells. In conclusion, our study demonstrated that a novel oxidative stress-related DElncRNA prognostic model performed favorably in predicting ESCC patient prognosis and benefits personalized clinical applications.

The possible molecular mechanism underlying the involvement of the variable shear factor QKI in the epithelial-mesenchymal transformation of oesophageal cancer.

OBJECTIVE: Based on the GEO, TCGA and GTEx databases, we reveal the possible molecular mechanism of the variable shear factor QKI in epithelial mesenchymal transformation (EMT) of oesophageal cancer. METHODS: Based on the TCGA and GTEx databases, the differential expression of the variable shear factor QKI in oesophageal cancer samples was analysed, and functional enrichment analysis of QKI was performed based on the TCGA-ESCA dataset. The percent-spliced in (PSI) data of oesophageal cancer samples were downloaded from the TCGASpliceSeq database, and the genes and variable splicing types that were significantly related to the expression of the variable splicing factor QKI were screened out. We further identified the significantly upregulated circRNAs and their corresponding coding genes in oesophageal cancer, screened the EMT-related genes that were significantly positively correlated with QKI expression, predicted the circRNA-miRNA binding relationship through the circBank database, predicted the miRNA-mRNA binding relationship through the TargetScan database, and finally obtained the circRNA-miRNA-mRNA network through which QKI promoted the EMT process. RESULTS: Compared with normal control tissue, QKI expression was significantly upregulated in tumour tissue samples of oesophageal cancer patients. High expression of QKI may promote the EMT process in oesophageal cancer. QKI promotes hsa_circ_0006646 and hsa_circ_0061395 generation by regulating the variable shear of BACH1 and PTK2. In oesophageal cancer, QKI may promote the production of the above two circRNAs by regulating variable splicing, and these circRNAs further competitively bind miRNAs to relieve the targeted inhibition of IL-11, MFAP2, MMP10, and MMP1 and finally promote the EMT process. CONCLUSION: Variable shear factor QKI promotes hsa_circ_0006646 and hsa_circ_0061395 generation, and downstream related miRNAs can relieve the targeted inhibition of EMT-related genes (IL11, MFAP2, MMP10, MMP1) and promote the occurrence and development of oesophageal cancer, providing a new theoretical basis for screening prognostic markers of oesophageal cancer patients.

Antibody-drug conjugates: the clinical development in gastric cancer.

Gastric cancer (GC) is a prevalent malignant tumor of the digestive system worldwide, ranking among the top five in terms of incidence and mortality. However, the clinical efficacy of conventional treatments for gastric cancer remains limited, with a median overall survival of approximately eight months for advanced cases. In recent years, researchers have increasingly focused on antibody-drug conjugates (ADCs) as a promising approach. ADCs are potent chemical drugs that selectively target cancer cells by binding to specific cell surface receptors with antibodies. Notably, ADCs have demonstrated promising results in clinical studies and have made significant strides in the treatment of gastric cancer. Currently, several ADCs are under investigation in clinical trials for gastric cancer patients, targeting various receptors such as EGFR, HER-2, HER-3, CLDN18.2, Mucin 1, among others. This review offers a comprehensive exploration of ADC drug characteristics and provides an overview of the research progress in ADC-based therapies for gastric cancer.

Associations between life-course household wealth mobility and adolescent physical growth, cognitive development and emotional and behavioral problems: A birth cohort in rural western China.

Background: Parental household wealth has been shown to be associated with offspring health conditions, while inconsistent associations were reported among generally healthy population especially in low- and middle- income countries (LMICs). Whether the household wealth upward mobility in LMICs would confer benefits to child health remains unknown. Methods: We conducted a prospective birth cohort of children born to mothers who participated in a randomized trial of antenatal micronutrient supplementation in rural western China. Household wealth were repeatedly assessed at pregnancy, mid-childhood and early adolescence using principal component analysis for household assets and dwelling characteristics. We used conditional gains and group-based trajectory modeling to assess the quantitative changes between two single-time points and relative mobility of household wealth over life-course, respectively. We performed generalized linear regressions to examine the associations of household wealth mobility indicators with adolescent height- (HAZ) and body mass index-for-age and sex z score (BAZ), scores of full-scale intelligent quotient (FSIQ) and emotional and behavioral problems. Results: A total of 1,188 adolescents were followed, among them 59.9% were male with a mean (SD) age of 11.7 (0.9) years old. Per SD conditional increase of household wealth z score from pregnancy to mid-childhood was associated with 0.11 (95% CI 0.04, 0.17) SD higher HAZ and 1.41 (95% CI 0.68, 2.13) points higher FSIQ at early adolescence. Adolescents from the household wealth Upward trajectory had a 0.25 (95% CI 0.03, 0.47) SD higher HAZ and 4.98 (95% CI 2.59, 7.38) points higher FSIQ than those in the Consistently low subgroup. Conclusion: Household wealth upward mobility particularly during early life has benefits on adolescent HAZ and cognitive development, which argues for government policies to implement social welfare programs to mitigate or reduce the consequences of early-life deprivations. Given the importance of household wealth in child health, it is recommended that socioeconomic circumstances should be routinely documented in the healthcare record in LMICs.

Effects of antenatal micronutrient supplementation regimens on adolescent emotional and behavioral problems: A 14-year follow-up of a double-blind, cluster-randomized controlled trial.

BACKGROUND & AIMS: Antenatal multiple micronutrient supplementation has been shown to have beneficial effects on birth outcomes and may improve child development. However, whether there is an effect of antenatal micronutrient supplementation strategies on offspring socioemotional outcomes remains unknown. We aimed to examine the effect of antenatal folic acid (FA), iron-folic acid (IFA), and multiple micronutrient (MMN) supplementation on adolescent emotional and behavioral outcomes. METHODS: We conducted a double-blind, cluster-randomized trial of antenatal micronutrient supplementation in rural western China between 2002 and 2006. Pregnant females were randomized by village to receive either daily (i) 400 µg FA, (ii) IFA containing 60 mg iron and 400 µg FA or (iii) MMN supplementation containing 30 mg iron, 400 µg FA plus 13 additional vitamins and minerals. A 14-year follow-up of their offspring was conducted in 2016. Adolescents were administered the locally adapted Youth Self-Report-2001 (YSR-2001) which produced internalizing, externalizing, and total behavior problem scores. We applied generalized estimating equations to assess the effect of the randomized regimens on YSR-2001 scores and explored the potential effect modification by household wealth and initial timing and duration of supplementation. RESULTS: A total of 1920 adolescents were included in the analysis, 1130 (58.9%) were male, and the mean (SD) age was 11.8 (0.78) years. Adolescents in IFA group had lower total (mean difference (MD): -2.89; 95% CI -5.73, -0.04) and externalizing (MD: -0.97; 95% CI -1.79, -0.15) problem scores as compared to those in FA group. There was no effect of MMN on behavior problem scores as compared to IFA and FA alone. Although, in effect modification analyses, MMN appeared to have greater beneficial effects in wealthier households than IFA and FA alone. CONCLUSIONS: Iron supplementation during pregnancy reduced adolescent emotional and behavioral problem scores which provides additional support for expanding coverage of iron-containing prenatal supplements in resource-limited settings. TRIAL REGISTRATION: isrctn. org Identifier: ISRCTN08850194.

The impact of early-life antibiotics and probiotics on gut microbial ecology and infant health outcomes: a Pregnancy and Birth Cohort in Northwest China (PBCC) study protocol.

BACKGROUND: Unreasonable use of antibiotics and probiotics can alter the gut ecology, leading to antibiotic resistance and suboptimal health outcomes during early life. Our study aims are to clarify the association among antibiotic and probiotic exposure in early life, the microecology of the gut microbiota, and the development of antibiotic resistance; to investigate the long-term impact of antibiotics and probiotics on the health outcomes of infants and young children; and to provide a theoretical basis for the rational use of antibiotics and probiotics from a life course perspective. METHODS: The study is a prospective, longitudinal birth cohort study conducted in Shaanxi Province, China from 2018 to 2024. A total of 3,000 eligible mother-child pairs will be enrolled from rural, suburban, and urban areas. The recruitment of the participants begins at pregnancy, and the newborns will be followed up for 2 years at successive timepoints: within 3 days after birth, 42 days after birth, and at 3, 6, 12, 18, and 24 months of age. Sociodemographic data, environmental exposures, dietary patterns, psychological conditions, and medical and drug histories are collected. Cognitive and behavioural development among infants and young children and questionnaires on antibiotic knowledge and behaviour among caregivers will be collected at 12 and 24 months of age. The faecal samples are collected and analysed by 16S rRNA high-throughput sequencing and quantitative PCR (qPCR) for antibiotic resistance genes. DISCUSSION: The findings will inform antibiotic and probiotic use for pregnant women and infants and contribute to establishing rational use strategies of antibiotics and probiotics for paediatricians, health practitioners, and drug administration policy-makers. TRIAL REGISTRATION: The study was registered on the Chinese Clinical Trial Registry (ChiCTR) platform, http://www.chictr.org.cn (Record ID: ChiCTR2100047531, June 20, 2021).

Small-cell lung cancer brain metastasis: From molecular mechanisms to diagnosis and treatment.

Lung cancer is the most malignant human cancer worldwide, also with the highest incidence rate. However, small-cell lung cancer (SCLC) accounts for 14 % of all lung cancer cases. Approximately 10 % of patients with SCLC have brain metastasis at the time of diagnosis, which is the leading cause of death of patients with SCLC worldwide. The median overall survival is only 4.9 months, and a long-tern cure exists for patients with SCLC brain metastasis due to limited common therapeutic options. Recent studies have enhanced our understanding of the molecular mechanisms leading to meningeal metastasis, and multimodality treatments have brought new hopes for a better cure for the disease. This review aimed to offer an insight into the cellular processes of different metastatic stages of SCLC revealed by the established animal models, and into the major diagnostic methods of SCLC. Additionally, it provided in-depth information on the recent advances in SCLC treatments, and highlighted several new models and biomarkers with promises to improve the prognosis of SCLC.

Head circumference trajectories during the first two years of life and cognitive development, emotional, and behavior problems in adolescence: a cohort study.

The associations of early-life head circumference (HC) with child neurodevelopmental and mental health among generally healthy population remain unclear. We aimed to examine the associations of early-life HC trajectories with cognitive development and emotional and behavioral problems in adolescence and to identify the HC growth-sensitive period. We conducted a prospective, community-based birth cohort study in rural western China, and 745 adolescents aged 10-14 years were followed between June and December 2016. We assessed their HC eight times during the first 2 years of life and their adolescent cognitive, emotional, and behavioral outcomes using the Wechsler Intelligence Scale for Children-IV and Youth Self-Report-2001, respectively. We applied group-based trajectory modeling to identify the HC trajectories and conditional growth to derive the HC growth-sensitive periods. We identified five distinct HC trajectories characterized as Start below average-then decrease (7.8% of the sample), Start below average-then increase (6.8%), Start average-then decrease (33%), Consistently average (38%), and Consistently above average (14%). Infants in the trajectory of consistently above average had higher cognitive scores in adolescence compared to those from suboptimal trajectories, with adjusted mean differences ranging from 2.84 to 8.99 points. The conditional gains showed that the HC growth-sensitive period was between 0 and 18 months for child cognition. We found null associations between HC measures and adolescent emotional and behavioral problem scores. CONCLUSION: Early-life HC trajectories were associated with adolescent cognitive development. HC may serve as an inexpensive screening tool to monitor child development at risk during the first 18 months, particularly in resource-limited settings. WHAT IS KNOWN: • Postnatal head circumference (HC) has been shown to be associated with cognitive development in infants who were born premature and/or fetal growth restriction, while inconsistent associations were reported among generally healthy populations, especially in low- and middle- income countries, challenging its utility in public health practices. WHAT IS NEW: • Adolescents in the HC growth trajectory of consistently above average had higher cognitive scores compared to those with other suboptimal trajectories, while null findings were observed for adolescent emotional and behavioral health. • HC may serve as an inexpensive screening tool to monitor child development at risk during the first 18 months of life, particularly in resource-limited settings.